Treatment Comparison in Rheumatoid Arthritis: Head-to-Head Trials and Innovative Study Designs

Table 1

Randomised controlled trials of biological disease-modifying anti-rheumatic drugs that have supported regulatory labeling.

	Trial	Study drug	Duration	Primary endpoints
MTX-naїve
abatacept*	AGREE [13]	ABT + MTX versus MTX	12 months	DAS28-CRP < 2.6 at 12 months; xRay progression at 12 months
adalimumab	PREMIER [14]	ADA + MTX versus MTX versus ADA	24 months	ACR50 at 12 months; xRay progression at 12 months
	OPTIMA [15]	ADA + MTX versus PL + MTX	6 months	DAS28-CRP < 3.2 at 78 wks; no xRay progression at 78 wks
certolizumab*	—
etanercept	ERA [16]	ETN versus MTX	12 months	overall ACR response at 6 months; xRay progression at 12 months
	COMET [17]	ETN + MTX versus MTX	24 months	DAS28 < 2.6 at 12 months; xRay progression at 12 months
golimumab	GO-BEFORE [18]	GOL + MTX versus PL + GOL versus PL + MTX	6 months	ACR50 at 6 months
infliximab	ASPIRE [19]	IFL + MTX versus PL + MTX	12 months	overall ACR response at 12 months; xRay progression at 12 months
rituximab**	IMAGE [20]	RTX + MTX versus MTX	12 months	xRay progression at 12 months
tocilizumab**	—
MTX/DMARD-IR
abatacept	AIM [21]	ABT + MTX versus PL + MTX	12 months	ACR20 at 6 months; HAQ-DI at 12 months; xRay progression at 12 months
	ATTEST [22]	ABT + MTX versus PL + MTX versus PL + INF	12 months	DAS28 at 6 months
adalimumab	ARMADA [23]	ADA + MTX versus PL + MTX	6 months	ACR20
	DE019 [24]	ADA + MTX versus PL + MTX	12 months	ACR20 at 6 months; HAQ-DI at 12 months; xRay progression at 12 months
certolizumab	RAPID-1 [25]	CER + MTX versus PL + MTX	12 months	ACR20 at 6 months; xRay progression at 12 months
	RAPID-2 [26]	CER + MTX versus PL + MTX	6 months	ACR20 at 6 months
	FAST4WARD [27]	CER versus PL	6 months	ACR20 at 6 months
etanercept	Weinblatt [28]	ETN + MTX versus PL + MTX	6 months	ACR20 at 6 months
	TEMPO [29]	ETN versus MTX versus ETN + MTX	12 months	overall ACR response at 6 months; xRay progression at 12 months
	ADORE [30]	ETN + MTX versus ETN	4 months	improvement of > 1.2 units in DAS28 at 4 months
golimumab	GO-FORWARD [31]	GOL + MTX versus PL + GOL versus PL + MTX	6 months	ACR20 at 14 weeks; HAQ-DI at 6 months
infliximab	ATTRACT [32]	IFL + MTX versus PL + MTX	30 weeks	ACR20 at 30 weeks
rituximab***	DANCER [33]	RTX + MTX versus PL + MTX	6 months	ACR20 at 6 months
	SERENE [34]	RTX + MTX versus PL + MTX	12 months	ACR20 at 6 months
	MIRROR [35]	RTX + MTX versus PL + MTX	12 months	ACR20 at 12 months
tocilizumab	OPTION [36]	TCZ + MTX versus PL + MTX	6 months	ACR20 at 6 months
	LITHE [37]	TCZ + MTX versus PL + MTX	24 months	HAQ-DI at 12 months; xRay progression at 12 months
	TOWARD [38]	TCZ + DMARD versus PL + DMARD	6 months	ACR20 at 6 months
	STREAM [39]	TCZ versus PL	3 months	ACR20 at 3 months
	ROSE [40]	TCZ + DMARD versus PL + DMARD	6 months	ACR20 at 6 months
Anti-TNF IR
abatacept	ATTAIN [41]	ABT + DMARD versus PL + DMARD	6 months	ACR20 at 6 months; HAQ-DI at 6 months
adalimumab	—
certolizumab	—
etanercept	—
golimumab	GO-AFTER [42]	GOL + DMARDs versus PL + DMARDs	6 months	ACR20 at 14 weeks
infliximab	OPPOSITE [43]	IFL + MTX versus ETN + MTX	n.d.	none
rituximab	REFLEX [44]	RTX + MTX versus PL + MTX	24 months	ACR20 at 6 months
tocilizumab	RADIATE [45]	TCZ + MTX versus PL + MTX	6 months	ACR20 at 6 months

∗approved by FDA, not approved by EMA in MTX-naїve patients.
∗∗not approved by neither FDA nor by EMA in MTX-naїve patients.
∗∗∗not approved by neither FDA nor by EMA in MTX-IR patients.
ABT: abatacept; ACR: American College of Rheumatology; ADA: adalimumab; CER: certolizumab; CRP: C-reactive protein; DAS: disease activity score; DMARD: disease modifying anti-rheumatic drug; ETN: etanercept; GOL: golimumab; HAQ-DI: Health Assessment Questionnaire Disability Index; IFL: infliximab; IR: irresponsive; MTX: methotrexate; PL: placebo; RTX: rituximab; TCZ: tocilizumab; TNF: tumor necrosis factor.